The glutathione S-transferase (GST)-tagged N protein of SARS-CoV-1 binds to endogenous NPM1 in HeLa cell lysates (Zeng Y et al. 2008). Co-immunoprecipitation assay further confirmed the interaction of NPM1 and the viral N protein in N-expressing HeLa cells. An in vitro phosphorylation assay using HeLa cell lysates showed that the binding of N protein inhibited the phosphorylation of NPM1 at Thr199 by CDK2 which can lead to cell cycle arrest (Zeng Y et al. 2008). SARS-CoV -1 N protein co-localized with the NPM1 protein in the perinuclear region of HeLa cells. NPM1 usually plays a role in nuclear import of the viral proteins to which it binds. It is unclear if the binding of SARS-CoV-1 N with NPM1 is involved with sub-cellular localization of N (Zeng Y et al, 2008). Similar findings were reported for the N protein of porcine epidemic diarrhea virus (PEDV), which belongs to the Alphacoronavirus genus in the Coronaviridae family (Shi D et al. 2017). Binding of the PEDV N protein to NPM1 prevented proteolytic cleavage of NPM1 by caspase-3 leading to increased cell survival (Shi D et al. 2017).

This Reactome event shows the interaction between SARS-CoV-1 N and host NPM1.